CA3060509A1 - Ciblage de cellules souches cancereuses hypoxiques (csc) a l'aide de doxycycline : implications pour ameliorer une therapie anti-angiogenique - Google Patents
Ciblage de cellules souches cancereuses hypoxiques (csc) a l'aide de doxycycline : implications pour ameliorer une therapie anti-angiogenique Download PDFInfo
- Publication number
- CA3060509A1 CA3060509A1 CA3060509A CA3060509A CA3060509A1 CA 3060509 A1 CA3060509 A1 CA 3060509A1 CA 3060509 A CA3060509 A CA 3060509A CA 3060509 A CA3060509 A CA 3060509A CA 3060509 A1 CA3060509 A1 CA 3060509A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- mitochondrial biogenesis
- doxycycline
- mitochondrial
- cscs
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 206010021143 Hypoxia Diseases 0.000 title claims abstract description 83
- 229960003722 doxycycline Drugs 0.000 title claims abstract description 27
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 26
- 230000001146 hypoxic effect Effects 0.000 title claims abstract description 23
- 201000011510 cancer Diseases 0.000 title claims abstract description 20
- 210000000130 stem cell Anatomy 0.000 title claims description 12
- 238000011122 anti-angiogenic therapy Methods 0.000 title description 5
- 230000008685 targeting Effects 0.000 title description 3
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 title 1
- 239000003112 inhibitor Substances 0.000 claims abstract description 48
- 230000008437 mitochondrial biogenesis Effects 0.000 claims abstract description 41
- 238000000034 method Methods 0.000 claims abstract description 27
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 claims abstract description 26
- 239000004098 Tetracycline Substances 0.000 claims abstract description 11
- 239000004037 angiogenesis inhibitor Substances 0.000 claims abstract description 11
- 235000019364 tetracycline Nutrition 0.000 claims abstract description 11
- 150000003522 tetracyclines Chemical class 0.000 claims abstract description 11
- 238000002512 chemotherapy Methods 0.000 claims abstract description 9
- -1 doxycycline Chemical class 0.000 claims abstract description 8
- 230000001235 sensitizing effect Effects 0.000 claims abstract description 7
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 14
- 239000005511 L01XE05 - Sorafenib Substances 0.000 claims description 14
- 229960003787 sorafenib Drugs 0.000 claims description 14
- DZLOHEOHWICNIL-QGZVFWFLSA-N (2R)-2-[6-(4-chlorophenoxy)hexyl]-2-oxiranecarboxylic acid ethyl ester Chemical compound C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)OCC)CO1 DZLOHEOHWICNIL-QGZVFWFLSA-N 0.000 claims description 13
- 229950006213 etomoxir Drugs 0.000 claims description 13
- CYXKNKQEMFBLER-UHFFFAOYSA-N perhexiline Chemical compound C1CCCNC1CC(C1CCCCC1)C1CCCCC1 CYXKNKQEMFBLER-UHFFFAOYSA-N 0.000 claims description 13
- 229960000989 perhexiline Drugs 0.000 claims description 13
- LDBPIZIYTBIRPM-VQHVLOKHSA-N phenyl (e)-3-(3,4-dihydroxyphenyl)prop-2-enoate Chemical compound C1=C(O)C(O)=CC=C1\C=C\C(=O)OC1=CC=CC=C1 LDBPIZIYTBIRPM-VQHVLOKHSA-N 0.000 claims description 12
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 claims description 10
- NZJKEVWTYMOYOR-UHFFFAOYSA-N 3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanylidene-1h-quinazolin-4-one Chemical compound C1=C(Cl)C(OC)=CC(N2C(C3=CC=CC=C3NC2=S)=O)=C1Cl NZJKEVWTYMOYOR-UHFFFAOYSA-N 0.000 claims description 10
- OOPDAHSJBRZRPH-UHFFFAOYSA-L Pyrvinium pamoate Chemical compound C1=CC2=CC(N(C)C)=CC=C2[N+](C)=C1C=CC(=C1C)C=C(C)N1C1=CC=CC=C1.C1=CC2=CC(N(C)C)=CC=C2[N+](C)=C1C=CC(=C1C)C=C(C)N1C1=CC=CC=C1.C12=CC=CC=C2C=C(C([O-])=O)C(O)=C1CC1=C(O)C(C([O-])=O)=CC2=CC=CC=C12 OOPDAHSJBRZRPH-UHFFFAOYSA-L 0.000 claims description 10
- 229960003159 atovaquone Drugs 0.000 claims description 10
- KUCQYCKVKVOKAY-CTYIDZIISA-N atovaquone Chemical compound C1([C@H]2CC[C@@H](CC2)C2=C(C(C3=CC=CC=C3C2=O)=O)O)=CC=C(Cl)C=C1 KUCQYCKVKVOKAY-CTYIDZIISA-N 0.000 claims description 10
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 claims description 10
- 229960004099 azithromycin Drugs 0.000 claims description 10
- QUIJNHUBAXPXFS-XLJNKUFUSA-N bedaquiline Chemical compound C1([C@H](C2=CC3=CC(Br)=CC=C3N=C2OC)[C@@](O)(CCN(C)C)C=2C3=CC=CC=C3C=CC=2)=CC=CC=C1 QUIJNHUBAXPXFS-XLJNKUFUSA-N 0.000 claims description 10
- 229960000508 bedaquiline Drugs 0.000 claims description 10
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 claims description 10
- 229940093265 berberine Drugs 0.000 claims description 10
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 claims description 10
- 229960003677 chloroquine Drugs 0.000 claims description 10
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 claims description 10
- RJMUSRYZPJIFPJ-UHFFFAOYSA-N niclosamide Chemical compound OC1=CC=C(Cl)C=C1C(=O)NC1=CC=C([N+]([O-])=O)C=C1Cl RJMUSRYZPJIFPJ-UHFFFAOYSA-N 0.000 claims description 10
- 229960001920 niclosamide Drugs 0.000 claims description 10
- 229960001077 pyrvinium pamoate Drugs 0.000 claims description 10
- IBLNKMRFIPWSOY-FNORWQNLSA-N stiripentol Chemical compound CC(C)(C)C(O)\C=C\C1=CC=C2OCOC2=C1 IBLNKMRFIPWSOY-FNORWQNLSA-N 0.000 claims description 10
- 229960001897 stiripentol Drugs 0.000 claims description 10
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 claims description 9
- SOVUOXKZCCAWOJ-HJYUBDRYSA-N (4s,4as,5ar,12ar)-9-[[2-(tert-butylamino)acetyl]amino]-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=C(NC(=O)CNC(C)(C)C)C(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O SOVUOXKZCCAWOJ-HJYUBDRYSA-N 0.000 claims description 9
- 229960002626 clarithromycin Drugs 0.000 claims description 9
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 claims description 9
- 229960004768 irinotecan Drugs 0.000 claims description 9
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 9
- 229960004023 minocycline Drugs 0.000 claims description 9
- 229960002180 tetracycline Drugs 0.000 claims description 9
- 229930101283 tetracycline Natural products 0.000 claims description 9
- 229960004089 tigecycline Drugs 0.000 claims description 9
- 229930012538 Paclitaxel Natural products 0.000 claims description 8
- 102000002938 Thrombospondin Human genes 0.000 claims description 8
- 108060008245 Thrombospondin Proteins 0.000 claims description 8
- 229960001592 paclitaxel Drugs 0.000 claims description 8
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 8
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 claims description 4
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 claims description 4
- CQOQDQWUFQDJMK-SSTWWWIQSA-N 2-methoxy-17beta-estradiol Chemical compound C([C@@H]12)C[C@]3(C)[C@@H](O)CC[C@H]3[C@@H]1CCC1=C2C=C(OC)C(O)=C1 CQOQDQWUFQDJMK-SSTWWWIQSA-N 0.000 claims description 4
- SGOOQMRIPALTEL-UHFFFAOYSA-N 4-hydroxy-N,1-dimethyl-2-oxo-N-phenyl-3-quinolinecarboxamide Chemical compound OC=1C2=CC=CC=C2N(C)C(=O)C=1C(=O)N(C)C1=CC=CC=C1 SGOOQMRIPALTEL-UHFFFAOYSA-N 0.000 claims description 4
- 102400000068 Angiostatin Human genes 0.000 claims description 4
- 108010079709 Angiostatins Proteins 0.000 claims description 4
- 108010079505 Endostatins Proteins 0.000 claims description 4
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 4
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 4
- 239000002147 L01XE04 - Sunitinib Substances 0.000 claims description 4
- 239000003798 L01XE11 - Pazopanib Substances 0.000 claims description 4
- MSHZHSPISPJWHW-UHFFFAOYSA-N O-(chloroacetylcarbamoyl)fumagillol Chemical compound O1C(CC=C(C)C)C1(C)C1C(OC)C(OC(=O)NC(=O)CCl)CCC21CO2 MSHZHSPISPJWHW-UHFFFAOYSA-N 0.000 claims description 4
- 102000004211 Platelet factor 4 Human genes 0.000 claims description 4
- 108090000778 Platelet factor 4 Proteins 0.000 claims description 4
- 102000003946 Prolactin Human genes 0.000 claims description 4
- 108010057464 Prolactin Proteins 0.000 claims description 4
- 108091008605 VEGF receptors Proteins 0.000 claims description 4
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 4
- 230000033115 angiogenesis Effects 0.000 claims description 4
- 230000000964 angiostatic effect Effects 0.000 claims description 4
- 239000005557 antagonist Substances 0.000 claims description 4
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 claims description 4
- 229960000397 bevacizumab Drugs 0.000 claims description 4
- WNRZHQBJSXRYJK-UHFFFAOYSA-N carboxyamidotriazole Chemical compound NC1=C(C(=O)N)N=NN1CC(C=C1Cl)=CC(Cl)=C1C(=O)C1=CC=C(Cl)C=C1 WNRZHQBJSXRYJK-UHFFFAOYSA-N 0.000 claims description 4
- 229960005167 everolimus Drugs 0.000 claims description 4
- 229960002897 heparin Drugs 0.000 claims description 4
- 229920000669 heparin Polymers 0.000 claims description 4
- 229960004130 itraconazole Drugs 0.000 claims description 4
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 claims description 4
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 claims description 4
- 229960000639 pazopanib Drugs 0.000 claims description 4
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 claims description 4
- 229940097325 prolactin Drugs 0.000 claims description 4
- 238000001959 radiotherapy Methods 0.000 claims description 4
- 229960002633 ramucirumab Drugs 0.000 claims description 4
- 229960003876 ranibizumab Drugs 0.000 claims description 4
- 229960003522 roquinimex Drugs 0.000 claims description 4
- 150000003431 steroids Chemical class 0.000 claims description 4
- 229960001796 sunitinib Drugs 0.000 claims description 4
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 claims description 4
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 claims description 4
- 229960005314 suramin Drugs 0.000 claims description 4
- ONDYALNGTUAJDX-UHFFFAOYSA-N tasquinimod Chemical compound OC=1C=2C(OC)=CC=CC=2N(C)C(=O)C=1C(=O)N(C)C1=CC=C(C(F)(F)F)C=C1 ONDYALNGTUAJDX-UHFFFAOYSA-N 0.000 claims description 4
- 229950001899 tasquinimod Drugs 0.000 claims description 4
- CXVCSRUYMINUSF-UHFFFAOYSA-N tetrathiomolybdate(2-) Chemical compound [S-][Mo]([S-])(=S)=S CXVCSRUYMINUSF-UHFFFAOYSA-N 0.000 claims description 4
- 229960003433 thalidomide Drugs 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims 10
- 229940127089 cytotoxic agent Drugs 0.000 claims 4
- 102400001047 Endostatin Human genes 0.000 claims 2
- 229940040944 tetracyclines Drugs 0.000 abstract description 2
- 230000004898 mitochondrial function Effects 0.000 abstract 1
- 230000007954 hypoxia Effects 0.000 description 60
- 210000004027 cell Anatomy 0.000 description 45
- 230000000694 effects Effects 0.000 description 31
- 210000003470 mitochondria Anatomy 0.000 description 29
- 230000001684 chronic effect Effects 0.000 description 27
- 230000002438 mitochondrial effect Effects 0.000 description 25
- 238000011282 treatment Methods 0.000 description 21
- NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical compound CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 18
- 230000004563 mammosphere formation Effects 0.000 description 15
- 102000005369 Aldehyde Dehydrogenase Human genes 0.000 description 12
- 108020002663 Aldehyde Dehydrogenase Proteins 0.000 description 12
- 238000013459 approach Methods 0.000 description 12
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 10
- 230000002503 metabolic effect Effects 0.000 description 9
- 229960000604 valproic acid Drugs 0.000 description 9
- 239000003642 reactive oxygen metabolite Substances 0.000 description 8
- VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 description 7
- 230000001154 acute effect Effects 0.000 description 7
- PMMURAAUARKVCB-UHFFFAOYSA-N alpha-D-ara-dHexp Natural products OCC1OC(O)CC(O)C1O PMMURAAUARKVCB-UHFFFAOYSA-N 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 108010058682 Mitochondrial Proteins Proteins 0.000 description 5
- 102000006404 Mitochondrial Proteins Human genes 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000036542 oxidative stress Effects 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 101000798951 Homo sapiens Mitochondrial import receptor subunit TOM20 homolog Proteins 0.000 description 4
- 102100020755 Hypoxia up-regulated protein 1 Human genes 0.000 description 4
- 101710120772 Hypoxia up-regulated protein 1 Proteins 0.000 description 4
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 4
- 108050009527 Hypoxia-inducible factor-1 alpha Proteins 0.000 description 4
- 102100034007 Mitochondrial import receptor subunit TOM20 homolog Human genes 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 230000034659 glycolysis Effects 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000007959 normoxia Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- PHIQHXFUZVPYII-ZCFIWIBFSA-O (R)-carnitinium Chemical compound C[N+](C)(C)C[C@H](O)CC(O)=O PHIQHXFUZVPYII-ZCFIWIBFSA-O 0.000 description 3
- 102100021403 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing], mitochondrial Human genes 0.000 description 3
- 102100021388 3-hydroxyisobutyrate dehydrogenase, mitochondrial Human genes 0.000 description 3
- 102000002735 Acyl-CoA Dehydrogenase Human genes 0.000 description 3
- 108010001058 Acyl-CoA Dehydrogenase Proteins 0.000 description 3
- 102100030362 Acyl-coenzyme A synthetase ACSM2B, mitochondrial Human genes 0.000 description 3
- 102100025845 Acyl-coenzyme A thioesterase 9, mitochondrial Human genes 0.000 description 3
- 102100024853 Carnitine O-palmitoyltransferase 2, mitochondrial Human genes 0.000 description 3
- 102100021645 Complex I assembly factor ACAD9, mitochondrial Human genes 0.000 description 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 101001041661 Homo sapiens 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing], mitochondrial Proteins 0.000 description 3
- 101000773360 Homo sapiens Acyl-coenzyme A synthetase ACSM2B, mitochondrial Proteins 0.000 description 3
- 101000720385 Homo sapiens Acyl-coenzyme A thioesterase 9, mitochondrial Proteins 0.000 description 3
- 101000909313 Homo sapiens Carnitine O-palmitoyltransferase 2, mitochondrial Proteins 0.000 description 3
- 101000677550 Homo sapiens Complex I assembly factor ACAD9, mitochondrial Proteins 0.000 description 3
- 101000760730 Homo sapiens Medium-chain specific acyl-CoA dehydrogenase, mitochondrial Proteins 0.000 description 3
- 101001111187 Homo sapiens NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial Proteins 0.000 description 3
- 101001098982 Homo sapiens Propionyl-CoA carboxylase beta chain, mitochondrial Proteins 0.000 description 3
- 101000929936 Homo sapiens Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial Proteins 0.000 description 3
- 101000661451 Homo sapiens Succinate-CoA ligase [GDP-forming] subunit beta, mitochondrial Proteins 0.000 description 3
- 101000760747 Homo sapiens Very long-chain specific acyl-CoA dehydrogenase, mitochondrial Proteins 0.000 description 3
- 102100030358 Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Human genes 0.000 description 3
- 102100024590 Medium-chain specific acyl-CoA dehydrogenase, mitochondrial Human genes 0.000 description 3
- 102100023964 NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial Human genes 0.000 description 3
- 102100039025 Propionyl-CoA carboxylase beta chain, mitochondrial Human genes 0.000 description 3
- 108010000605 Ribosomal Proteins Proteins 0.000 description 3
- 102000002278 Ribosomal Proteins Human genes 0.000 description 3
- 102100035766 Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial Human genes 0.000 description 3
- 102100037788 Succinate-CoA ligase [GDP-forming] subunit beta, mitochondrial Human genes 0.000 description 3
- 102100024591 Very long-chain specific acyl-CoA dehydrogenase, mitochondrial Human genes 0.000 description 3
- 229930003268 Vitamin C Natural products 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 229960004203 carnitine Drugs 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 3
- 235000019154 vitamin C Nutrition 0.000 description 3
- 239000011718 vitamin C Substances 0.000 description 3
- MNULEGDCPYONBU-WMBHJXFZSA-N (1r,4s,5e,5'r,6'r,7e,10s,11r,12s,14r,15s,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trio Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](C[C@H](C)O)O1 MNULEGDCPYONBU-WMBHJXFZSA-N 0.000 description 2
- MNULEGDCPYONBU-DJRUDOHVSA-N (1s,4r,5z,5'r,6'r,7e,10s,11r,12s,14r,15s,18r,19r,20s,21e,26r,27s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers O([C@H]1CC[C@H](\C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)C(C)C(=O)[C@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)OC([C@H]2C)C1C)CC)[C@]12CC[C@@H](C)[C@@H](CC(C)O)O1 MNULEGDCPYONBU-DJRUDOHVSA-N 0.000 description 2
- MNULEGDCPYONBU-YNZHUHFTSA-N (4Z,18Z,20Z)-22-ethyl-7,11,14,15-tetrahydroxy-6'-(2-hydroxypropyl)-5',6,8,10,12,14,16,28,29-nonamethylspiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-oxane]-3,9,13-trione Polymers CC1C(C2C)OC(=O)\C=C/C(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)C\C=C/C=C\C(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-YNZHUHFTSA-N 0.000 description 2
- MNULEGDCPYONBU-VVXVDZGXSA-N (5e,5'r,7e,10s,11r,12s,14s,15r,16r,18r,19s,20r,21e,26r,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers C([C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)OC([C@H]1C)[C@H]2C)\C=C\C=C\C(CC)CCC2OC21CC[C@@H](C)C(C[C@H](C)O)O2 MNULEGDCPYONBU-VVXVDZGXSA-N 0.000 description 2
- FLCWJWNCSHIREG-UHFFFAOYSA-N 2-(diethylamino)benzaldehyde Chemical compound CCN(CC)C1=CC=CC=C1C=O FLCWJWNCSHIREG-UHFFFAOYSA-N 0.000 description 2
- 102100024385 28S ribosomal protein S35, mitochondrial Human genes 0.000 description 2
- 108020003281 3-hydroxyisobutyrate dehydrogenase Proteins 0.000 description 2
- 102100039776 39S ribosomal protein L4, mitochondrial Human genes 0.000 description 2
- 102100033750 39S ribosomal protein L47, mitochondrial Human genes 0.000 description 2
- MNULEGDCPYONBU-UHFFFAOYSA-N 4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers CC1C(C2C)OC(=O)C=CC(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)CC=CC=CC(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-UHFFFAOYSA-N 0.000 description 2
- 102100038222 60 kDa heat shock protein, mitochondrial Human genes 0.000 description 2
- 102100028814 ATP synthase mitochondrial F1 complex assembly factor 1 Human genes 0.000 description 2
- 102100027782 ATP synthase-coupling factor 6, mitochondrial Human genes 0.000 description 2
- 102100031162 Collagen alpha-1(XVIII) chain Human genes 0.000 description 2
- 101710088194 Dehydrogenase Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 2
- 241001559542 Hippocampus hippocampus Species 0.000 description 2
- 101000727483 Homo sapiens 28S ribosomal protein S28, mitochondrial Proteins 0.000 description 2
- 101000689823 Homo sapiens 28S ribosomal protein S35, mitochondrial Proteins 0.000 description 2
- 101000667416 Homo sapiens 39S ribosomal protein L4, mitochondrial Proteins 0.000 description 2
- 101000733895 Homo sapiens 39S ribosomal protein L47, mitochondrial Proteins 0.000 description 2
- 101000883686 Homo sapiens 60 kDa heat shock protein, mitochondrial Proteins 0.000 description 2
- 101000789413 Homo sapiens ATP synthase mitochondrial F1 complex assembly factor 1 Proteins 0.000 description 2
- 101000936965 Homo sapiens ATP synthase-coupling factor 6, mitochondrial Proteins 0.000 description 2
- 101001083553 Homo sapiens Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Proteins 0.000 description 2
- 101000966742 Homo sapiens Leucine-rich PPR motif-containing protein, mitochondrial Proteins 0.000 description 2
- 101001064870 Homo sapiens Lon protease homolog, mitochondrial Proteins 0.000 description 2
- 101000674040 Homo sapiens Serine-tRNA ligase, mitochondrial Proteins 0.000 description 2
- 101000903318 Homo sapiens Stress-70 protein, mitochondrial Proteins 0.000 description 2
- 101000860835 Homo sapiens Ubiquinone biosynthesis protein COQ9, mitochondrial Proteins 0.000 description 2
- 102100040589 Leucine-rich PPR motif-containing protein, mitochondrial Human genes 0.000 description 2
- 108090000364 Ligases Proteins 0.000 description 2
- 102000003960 Ligases Human genes 0.000 description 2
- 102100031955 Lon protease homolog, mitochondrial Human genes 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 2
- 108091006703 SLC25A1 Proteins 0.000 description 2
- 102100040597 Serine-tRNA ligase, mitochondrial Human genes 0.000 description 2
- 102100022760 Stress-70 protein, mitochondrial Human genes 0.000 description 2
- 102100036216 Tricarboxylate transport protein, mitochondrial Human genes 0.000 description 2
- 102100025336 Tyrosine-tRNA ligase, mitochondrial Human genes 0.000 description 2
- 102100028230 Ubiquinone biosynthesis protein COQ9, mitochondrial Human genes 0.000 description 2
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 238000011254 conventional chemotherapy Methods 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000006539 extracellular acidification Effects 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 230000004907 flux Effects 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 230000022886 mitochondrial translation Effects 0.000 description 2
- 229930191479 oligomycin Natural products 0.000 description 2
- MNULEGDCPYONBU-AWJDAWNUSA-N oligomycin A Polymers O([C@H]1CC[C@H](/C=C/C=C/C[C@@H](C)[C@H](O)[C@@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)O[C@@H]([C@@H]2C)[C@@H]1C)CC)[C@@]12CC[C@H](C)[C@H](C[C@@H](C)O)O1 MNULEGDCPYONBU-AWJDAWNUSA-N 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000036284 oxygen consumption Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- NGGMYCMLYOUNGM-UHFFFAOYSA-N (-)-fumagillin Natural products O1C(CC=C(C)C)C1(C)C1C(OC)C(OC(=O)C=CC=CC=CC=CC(O)=O)CCC21CO2 NGGMYCMLYOUNGM-UHFFFAOYSA-N 0.000 description 1
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
- 229940044192 2-hydroxyethyl methacrylate Drugs 0.000 description 1
- 101710107190 3-hydroxyisobutyrate dehydrogenase, mitochondrial Proteins 0.000 description 1
- 102100035923 4-aminobutyrate aminotransferase, mitochondrial Human genes 0.000 description 1
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 1
- 102100026926 60S ribosomal protein L4 Human genes 0.000 description 1
- 102100040439 Adenylate kinase 4, mitochondrial Human genes 0.000 description 1
- UIFFUZWRFRDZJC-UHFFFAOYSA-N Antimycin A1 Natural products CC1OC(=O)C(CCCCCC)C(OC(=O)CC(C)C)C(C)OC(=O)C1NC(=O)C1=CC=CC(NC=O)=C1O UIFFUZWRFRDZJC-UHFFFAOYSA-N 0.000 description 1
- NQWZLRAORXLWDN-UHFFFAOYSA-N Antimycin-A Natural products CCCCCCC(=O)OC1C(C)OC(=O)C(NC(=O)c2ccc(NC=O)cc2O)C(C)OC(=O)C1CCCC NQWZLRAORXLWDN-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102100030297 Calcium uptake protein 1, mitochondrial Human genes 0.000 description 1
- 102100034279 Calcium-binding mitochondrial carrier protein Aralar2 Human genes 0.000 description 1
- 102100036290 Calcium-binding mitochondrial carrier protein SCaMC-1 Human genes 0.000 description 1
- 101710189678 Calcium-binding mitochondrial carrier protein SCaMC-1 Proteins 0.000 description 1
- BMZRVOVNUMQTIN-UHFFFAOYSA-N Carbonyl Cyanide para-Trifluoromethoxyphenylhydrazone Chemical compound FC(F)(F)OC1=CC=C(NN=C(C#N)C#N)C=C1 BMZRVOVNUMQTIN-UHFFFAOYSA-N 0.000 description 1
- 102100037021 Citrate synthase, mitochondrial Human genes 0.000 description 1
- 101710195882 Citrate synthase, mitochondrial Proteins 0.000 description 1
- 102100023376 Corrinoid adenosyltransferase Human genes 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 102100024745 DNA-directed RNA polymerase, mitochondrial Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 102100033189 Diablo IAP-binding mitochondrial protein Human genes 0.000 description 1
- 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Natural products O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 1
- 102100031627 Evolutionarily conserved signaling intermediate in Toll pathway, mitochondrial Human genes 0.000 description 1
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 1
- 229940124602 FDA-approved drug Drugs 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 102100025960 Glutaminase kidney isoform, mitochondrial Human genes 0.000 description 1
- 101710136238 Glutaminase kidney isoform, mitochondrial Proteins 0.000 description 1
- 102000042775 Heat shock protein 70 family Human genes 0.000 description 1
- 108091082017 Heat shock protein 70 family Proteins 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 101001000686 Homo sapiens 4-aminobutyrate aminotransferase, mitochondrial Proteins 0.000 description 1
- 101000991050 Homo sapiens Calcium uptake protein 1, mitochondrial Proteins 0.000 description 1
- 101001114650 Homo sapiens Corrinoid adenosyltransferase Proteins 0.000 description 1
- 101000686765 Homo sapiens DNA-directed RNA polymerase, mitochondrial Proteins 0.000 description 1
- 101000871228 Homo sapiens Diablo IAP-binding mitochondrial protein Proteins 0.000 description 1
- 101000866489 Homo sapiens Evolutionarily conserved signaling intermediate in Toll pathway, mitochondrial Proteins 0.000 description 1
- 101001042038 Homo sapiens Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial Proteins 0.000 description 1
- 101000985328 Homo sapiens Methenyltetrahydrofolate cyclohydrolase Proteins 0.000 description 1
- 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 1
- 101001117146 Homo sapiens [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 101710150008 Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Proteins 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- 102100021311 Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial Human genes 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 101710130653 Lon protease homolog Proteins 0.000 description 1
- 102100028687 Methenyltetrahydrofolate cyclohydrolase Human genes 0.000 description 1
- 102100021769 Mitochondrial 2-oxoglutarate/malate carrier protein Human genes 0.000 description 1
- 101710142211 Mitochondrial 2-oxoglutarate/malate carrier protein Proteins 0.000 description 1
- 102100023727 Mitochondrial antiviral-signaling protein Human genes 0.000 description 1
- 101710142315 Mitochondrial antiviral-signaling protein Proteins 0.000 description 1
- 102100030105 Mitochondrial ornithine transporter 2 Human genes 0.000 description 1
- 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 1
- 102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 102100038943 NAD(P) transhydrogenase, mitochondrial Human genes 0.000 description 1
- 101710110504 NADH dehydrogenase [ubiquinone] flavoprotein 2 Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 101710180724 Propionyl-CoA carboxylase beta chain Proteins 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 108091006711 SLC25A2 Proteins 0.000 description 1
- 108010030161 Serine-tRNA ligase Proteins 0.000 description 1
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
- 102000005488 Thioesterase Human genes 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108091008852 Waterwitch Proteins 0.000 description 1
- 102100024148 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial Human genes 0.000 description 1
- BOPGDPNILDQYTO-NDOGXIPWSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2r,3r,4r,5r)-5-(3-carbamoyl-4h-pyridin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NDOGXIPWSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- UIFFUZWRFRDZJC-SBOOETFBSA-N antimycin A Chemical compound C[C@H]1OC(=O)[C@H](CCCCCC)[C@@H](OC(=O)CC(C)C)[C@H](C)OC(=O)[C@H]1NC(=O)C1=CC=CC(NC=O)=C1O UIFFUZWRFRDZJC-SBOOETFBSA-N 0.000 description 1
- PVEVXUMVNWSNIG-UHFFFAOYSA-N antimycin A3 Natural products CC1OC(=O)C(CCCC)C(OC(=O)CC(C)C)C(C)OC(=O)C1NC(=O)C1=CC=CC(NC=O)=C1O PVEVXUMVNWSNIG-UHFFFAOYSA-N 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 230000006617 autophagic digestion Effects 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008436 biogenesis Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- WYUSVOMTXWRGEK-HBWVYFAYSA-N cefpodoxime Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(O)=O)C(=O)C(=N/OC)\C1=CSC(N)=N1 WYUSVOMTXWRGEK-HBWVYFAYSA-N 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 108010084210 citrin Proteins 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- NGGMYCMLYOUNGM-CSDLUJIJSA-N fumagillin Chemical compound C([C@H]([C@H]([C@@H]1[C@]2(C)[C@H](O2)CC=C(C)C)OC)OC(=O)\C=C\C=C\C=C\C=C\C(O)=O)C[C@@]21CO2 NGGMYCMLYOUNGM-CSDLUJIJSA-N 0.000 description 1
- 229960000936 fumagillin Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 230000021125 mitochondrion degradation Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000019261 negative regulation of glycolysis Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 238000005312 nonlinear dynamic Methods 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 230000007055 protein processing involved in protein targeting to mitochondrion Effects 0.000 description 1
- 238000004725 rapid separation liquid chromatography Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 108090000893 ribosomal protein L4 Proteins 0.000 description 1
- 229940080817 rotenone Drugs 0.000 description 1
- JUVIOZPCNVVQFO-UHFFFAOYSA-N rotenone Natural products O1C2=C3CC(C(C)=C)OC3=CC=C2C(=O)C2C1COC1=C2C=C(OC)C(OC)=C1 JUVIOZPCNVVQFO-UHFFFAOYSA-N 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 108020002982 thioesterase Proteins 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000007998 vessel formation Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/65—Tetracyclines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La présente invention concerne des inhibiteurs de la fonction mitochondriale. L'invention concerne également des méthodes de traitement de cellules cancéreuses hypoxiques à l'aide d'agents anti-angiogéniques et d'inhibiteurs de la biogenèse mitochondriale. Des tétracyclines, telles que la doxycycline, peuvent servir d'inhibiteurs de la biogenèse mitochondriale. L'invention concerne également des méthodes de sensibilisation de cellules cancéreuses hypoxiques à au moins une chimiothérapie par administration d'un inhibiteur de la biogenèse mitochondriale avec la chimiothérapie.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762488483P | 2017-04-21 | 2017-04-21 | |
| US62/488,483 | 2017-04-21 | ||
| PCT/US2018/028601 WO2018195446A1 (fr) | 2017-04-21 | 2018-04-20 | Ciblage de cellules souches cancéreuses hypoxiques (csc) à l'aide de doxycycline : implications pour améliorer une thérapie anti-angiogénique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3060509A1 true CA3060509A1 (fr) | 2018-10-25 |
Family
ID=63856149
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3060509A Pending CA3060509A1 (fr) | 2017-04-21 | 2018-04-20 | Ciblage de cellules souches cancereuses hypoxiques (csc) a l'aide de doxycycline : implications pour ameliorer une therapie anti-angiogenique |
Country Status (4)
| Country | Link |
|---|---|
| US (2) | US11229657B2 (fr) |
| EP (1) | EP3612177A4 (fr) |
| CA (1) | CA3060509A1 (fr) |
| WO (1) | WO2018195446A1 (fr) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11197872B2 (en) | 2017-04-21 | 2021-12-14 | Lunella Biotech, Inc. | Vitamin C and doxycycline: a synthetic lethal combination therapy for eradicating cancer stem cells (CSCs) |
| CA3060509A1 (fr) | 2017-04-21 | 2018-10-25 | Federica Sotgia | Ciblage de cellules souches cancereuses hypoxiques (csc) a l'aide de doxycycline : implications pour ameliorer une therapie anti-angiogenique |
| MX2019013735A (es) | 2017-05-19 | 2020-01-15 | Lunella Biotech Inc | Antimitoscinas: inhibidores especificos de la biogenesis mitocondrial para erradicar celulas madre cancerosas. |
| CA3063450A1 (fr) | 2017-05-19 | 2018-11-22 | Lunella Biotech, Inc. | Diagnostic compagnon pour inhibiteurs mitochondriaux |
| CN110913854B (zh) | 2017-06-26 | 2023-04-28 | 卢内拉生物技术有限公司 | mitoketoscin：靶向癌细胞中酮代谢的基于线粒体的治疗剂 |
| CN111053900B (zh) * | 2019-11-19 | 2022-05-03 | 南京大学射阳高新技术研究院 | 一种靶向肿瘤、提高放疗敏感性的血小板载药体系及其制备方法 |
Family Cites Families (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3517067A (en) | 1964-02-11 | 1970-06-23 | Eastman Kodak Co | Syntheses of quaternary phosphonium salts |
| EP0310361A3 (fr) | 1987-09-30 | 1989-05-24 | Beckman Instruments, Inc. | Conjugat tridenté et méthode de sa mise en oeuvre |
| SI9011409A (en) | 1990-07-18 | 1995-10-31 | Pliva Pharm & Chem Works | O-methyl azitromycin derivates, methods and intermediates for their preparation and methods for preparation of pharmaceuticals products which comprise them |
| EP0656422B1 (fr) | 1993-11-05 | 2000-04-26 | Amersham Pharmacia Biotech UK Limited | Essai de chloramphenicol-acetyl-transférase (CAT) |
| WO1995015770A1 (fr) | 1993-12-09 | 1995-06-15 | Neorx Corporation | Procedes et composes de preciblage |
| US5441939A (en) | 1994-03-04 | 1995-08-15 | Pfizer Inc. | 3"-desmethoxy derivatives of erythromycin and azithromycin |
| EP0758549A4 (fr) | 1994-04-26 | 1997-07-02 | Nobuhiro Narita | Composition medicinale servant de medicament contre le cancer bronchopulmonaire "non a petites cellules" |
| US6165999A (en) | 1995-05-03 | 2000-12-26 | Pfizer Inc | Tetracycline derivatives |
| US6576636B2 (en) | 1996-05-22 | 2003-06-10 | Protarga, Inc. | Method of treating a liver disorder with fatty acid-antiviral agent conjugates |
| US5837696A (en) | 1997-01-15 | 1998-11-17 | The Research Foundation Of State University Of New York | Method of inhibiting cancer growth |
| WO1999026582A2 (fr) | 1997-11-25 | 1999-06-03 | University Of Otago | Composes cibles vers les mitochondries |
| ATE275151T1 (de) | 1998-03-03 | 2004-09-15 | Pfizer Prod Inc | 3,6-ketal-makrolidantibiotika |
| AUPP437698A0 (en) | 1998-06-30 | 1998-07-23 | Baumgart, Karl | Methods for treatment of coronary, carotid and other vascular disease |
| US6858598B1 (en) | 1998-12-23 | 2005-02-22 | G. D. Searle & Co. | Method of using a matrix metalloproteinase inhibitor and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
| US7485298B2 (en) | 2002-05-23 | 2009-02-03 | Michael Powell | Diagnosis and treatment of human dormancy-related sequellae |
| ES2395082T3 (es) | 2003-01-27 | 2013-02-08 | Endocyte, Inc. | Conjugado de folato-vinblastina como medicamento |
| US20070105937A1 (en) | 2003-12-22 | 2007-05-10 | Miguel Pappolla | Indole-3-propionamide and derivatives thereof |
| EP1555021A1 (fr) | 2004-01-16 | 2005-07-20 | National Health Research Institutes | Combinaisons d'un inhibiteur de la voie du mévalonate et d'un agoniste PPAR-gamma pour le traitement du cancer |
| US20050256081A1 (en) | 2004-02-26 | 2005-11-17 | Peyman Gholam A | Tetracycline derivatives for the treatment of ocular pathologies |
| US20060083727A1 (en) | 2004-07-15 | 2006-04-20 | Nanobac Pharmaceuticals, Inc. | Methods and compositions for the treatment of diseases characterized by calcification and/or plaque formation |
| TW200616604A (en) | 2004-08-26 | 2006-06-01 | Nicholas Piramal India Ltd | Nitric oxide releasing prodrugs containing bio-cleavable linker |
| US7989600B2 (en) | 2005-01-14 | 2011-08-02 | Glaxosmithkline Istrazivacki Centar Zagreb D.O.O. | Macrolide compounds containing biotin and photo-affinity group for macrolide target identification |
| JP5177429B2 (ja) | 2005-07-18 | 2013-04-03 | バイパー サイエンシズ，インコーポレイティド | 癌の治療 |
| AU2007212025A1 (en) * | 2006-02-06 | 2007-08-16 | Conor Medsystems, Inc. | Drug delivery stent with extended in vivo drug release |
| CA2652926A1 (fr) | 2006-05-26 | 2007-12-06 | Bayer Healthcare Llc | Associations de medicaments comportant des urees de diaryle substituees pour le traitement du cancer |
| JP2009539769A (ja) | 2006-06-02 | 2009-11-19 | アリアド ジーン セラピューティクス インコーポレイテッド | カペシタビン併用療法 |
| DK2074211T3 (da) | 2006-09-06 | 2013-06-17 | Medical Res Council | DNA polymeraser til inkorporation af farvestof-mærkede nukleotid-analoger |
| CA2674238A1 (fr) | 2006-10-30 | 2008-05-08 | Southern Research Institute | Interaction nbs1-atm de ciblage destinee a sensibiliser les cellules cancereuses a la radiotherapie et a la chimiotherapie |
| US9675578B2 (en) | 2006-12-14 | 2017-06-13 | Abraxis Bioscience, Llc | Breast cancer therapy based on hormone receptor status with nanoparticles comprising taxane |
| US8075902B2 (en) | 2007-01-03 | 2011-12-13 | Michael Powell | Diagnosis and treatment of cancer related to human dormancy |
| DE102007025423A1 (de) | 2007-05-30 | 2008-12-04 | Friedrich-Schiller-Universität Jena | Triphenylphosphonium-Derivate zum gezielten Transport und Freisetzen von Substanzen in Mitochondrien sowie Verfahren zu deren Verwendung |
| US8647673B2 (en) | 2007-07-24 | 2014-02-11 | Wayne State University | Nanoparticles for imaging and treating chlamydial infection |
| WO2009036108A1 (fr) * | 2007-09-13 | 2009-03-19 | Children's Medical Center Corporation | Procédés et compositions pour inhiber une fuite vasculaire |
| WO2009038656A1 (fr) | 2007-09-17 | 2009-03-26 | Kosta Steliou | Agents thérapeutiques antioxydants ciblant les mitochondries |
| CA2700257A1 (fr) | 2007-10-02 | 2009-04-09 | Hartmut Land | Methodes et compositions associees aux reponses synergiques aux mutations oncogenes |
| WO2010121177A2 (fr) | 2009-04-17 | 2010-10-21 | Colby Pharmaceutical Company | Compositions pharmaceutiquement actives comprenant des modulateurs de stress oxydatif (osm), nouvelles entités chimiques, compositions et utilisations |
| KR20120080579A (ko) | 2009-08-25 | 2012-07-17 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 암 치료와 예방에 있어 메트포르민의 사용 |
| CN109224064A (zh) | 2009-12-04 | 2019-01-18 | 昂科免疫有限公司 | 低氧诱导因子抑制剂的用途 |
| US20120141467A1 (en) | 2010-12-03 | 2012-06-07 | Schneider Daniel J | Ascorbic acid to treat chronic obstructive lung diseases and non-Hodgkin's lymphoma |
| US20120258937A1 (en) * | 2011-04-08 | 2012-10-11 | Fox Chase Cancer Center | Targeting Estrogen Receptors in the Treatment of Lymphangioleiomyomatosis |
| WO2012177986A2 (fr) | 2011-06-22 | 2012-12-27 | Vyome Biosciences | Promédicaments antifongiques et antibactériens à base d'un conjugué |
| EP3111937B1 (fr) * | 2011-07-08 | 2020-06-17 | Helmholtz-Zentrum für Infektionsforschung GmbH | Médicament pour le traitement du cancer du foie |
| US9801922B2 (en) | 2011-08-03 | 2017-10-31 | University Of Iowa Research Foundation | Compositions and methods of treating cancer |
| US9180134B2 (en) | 2011-08-18 | 2015-11-10 | Ecole Polytechnique Federale De Lausanne (Epel) | Mitochondrial ribosomal proteins as aging regulators |
| US9775855B2 (en) | 2011-09-14 | 2017-10-03 | Thomas J. Lewis | Compositions comprising macrolide and tetracycline and their uses |
| SG11201404888SA (en) * | 2012-02-17 | 2014-09-26 | Pharmacyclics Inc | Combinations of histone deacetylase inhibitor and pazopanib and uses thereof |
| CA2866080C (fr) | 2012-03-01 | 2021-01-19 | University Of Cincinnati | Composes actives par dro en tant que therapies anti-cancer selectives |
| WO2014029016A1 (fr) * | 2012-08-24 | 2014-02-27 | University Health Network | Composition comprenant une glycylcycline et un inhibiteur de tyrosine kinase pour le traitement du cancer |
| US9526795B2 (en) | 2012-08-28 | 2016-12-27 | Annam Biosciences, Llc | N-BOC-dendrimers and their conjugates |
| WO2014036654A1 (fr) | 2012-09-06 | 2014-03-13 | Mcmaster University | Composés et procédés pour le ciblage sélectif de cellules souches cancéreuses |
| US20140106004A1 (en) | 2012-10-12 | 2014-04-17 | Bing Lou Wong | Hemoglobin-based oxygen carrier-containing pharmaceutical composition for cancer targeting treatment and prevention of cancer recurrence |
| US9636329B2 (en) | 2012-11-06 | 2017-05-02 | Northwestern University | Methods of treating cancer with glut inhibitors and oxidative phosphorylation inhibitors |
| CN105142631A (zh) | 2013-01-14 | 2015-12-09 | 健康诊所有限公司 | 抗癌药物和用途 |
| US9937161B2 (en) | 2013-03-06 | 2018-04-10 | The General Hospital Corporation | Combinatorial compositions and methods for treatment of melanoma |
| JP6375091B2 (ja) | 2013-04-24 | 2018-08-15 | ノイジル、ジリ | 腫瘍性疾患であって特に高ｈｅｒ２タンパク質レベルの腫瘍性疾患を治療するためのタモキシフェン誘導体 |
| US10004809B2 (en) | 2013-07-01 | 2018-06-26 | University Of Georgia Research Foundation Inc. | Precise delivery of therapeutic agents to cell mitochondria for anti-cancer therapy |
| CN105792823B (zh) * | 2013-11-01 | 2019-11-12 | 皮特尼制药股份有限公司 | 治疗恶性肿瘤的药物组合 |
| CA2843943A1 (fr) | 2014-02-20 | 2014-05-28 | Pankaj Modi | Formules orales d'agents chimiotherapeutiques |
| US10398663B2 (en) | 2014-03-14 | 2019-09-03 | University Of Georgia Research Foundation, Inc. | Mitochondrial delivery of 3-bromopyruvate |
| US20170224730A1 (en) | 2014-06-10 | 2017-08-10 | Institute For Myeloma & Bone Cancer Research | Anti-cancer effects of proteasome inhibitors in combination with glucocorticoids, arsenic containing compounds, and ascorbic acid |
| GB201414806D0 (en) | 2014-08-20 | 2014-10-01 | Ucl Business Plc | Cyclosporin conjugates |
| US10413558B2 (en) | 2014-10-17 | 2019-09-17 | Targeted Therapies Research And Consulting Center Sprl | Multi-ingredient pharmaceutical composition for use in cancer therapy |
| JP6439931B2 (ja) | 2015-02-26 | 2018-12-19 | 大日本印刷株式会社 | 吸着搬送装置および吸着搬送方法 |
| RU2727474C2 (ru) | 2015-10-06 | 2020-07-21 | Редхилл Байофарма Лтд. | Виды комбинированной терапии для лечения рака |
| KR20190045213A (ko) | 2016-08-11 | 2019-05-02 | 더 카운실 오브 더 퀸즐랜드 인스티튜트 오브 메디컬 리서치 | 면역-조절 화합물 |
| US20190365830A1 (en) | 2017-01-18 | 2019-12-05 | Evelo Biosciences, Inc. | Methods of treating cancer |
| US20200121739A1 (en) | 2017-01-18 | 2020-04-23 | Evelo Biosciences, Inc. | Bacteria for treating cancer |
| CA3060509A1 (fr) * | 2017-04-21 | 2018-10-25 | Federica Sotgia | Ciblage de cellules souches cancereuses hypoxiques (csc) a l'aide de doxycycline : implications pour ameliorer une therapie anti-angiogenique |
| US11197872B2 (en) | 2017-04-21 | 2021-12-14 | Lunella Biotech, Inc. | Vitamin C and doxycycline: a synthetic lethal combination therapy for eradicating cancer stem cells (CSCs) |
| WO2018202910A1 (fr) | 2017-05-05 | 2018-11-08 | Fondazione Istituto Italiano Di Tecnologia | Combinaison d'un antibiotique et d'un inhibiteur de bcl-2 et utilisations correspondantes |
| CA3063450A1 (fr) | 2017-05-19 | 2018-11-22 | Lunella Biotech, Inc. | Diagnostic compagnon pour inhibiteurs mitochondriaux |
| MX2019013735A (es) | 2017-05-19 | 2020-01-15 | Lunella Biotech Inc | Antimitoscinas: inhibidores especificos de la biogenesis mitocondrial para erradicar celulas madre cancerosas. |
| WO2018218242A1 (fr) | 2017-05-26 | 2018-11-29 | Epicentrx, Inc. | Méthodes et compositions pour polythérapie |
| CR20200238A (es) | 2017-11-24 | 2020-12-04 | Lunella Biotech Inc | Compuestos derivados de trifenilfosfonio para erradicar células madre cancerosas |
| US11559527B2 (en) | 2017-12-20 | 2023-01-24 | Lunella Biotech, Inc. | Targeting mitochondrial fission through mDIVI-1 derivatives |
-
2018
- 2018-04-20 CA CA3060509A patent/CA3060509A1/fr active Pending
- 2018-04-20 US US16/606,849 patent/US11229657B2/en active Active
- 2018-04-20 WO PCT/US2018/028601 patent/WO2018195446A1/fr active Search and Examination
- 2018-04-20 EP EP18787729.5A patent/EP3612177A4/fr not_active Withdrawn
-
2021
- 2021-12-13 US US17/549,475 patent/US20220096502A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2018195446A1 (fr) | 2018-10-25 |
| EP3612177A4 (fr) | 2021-01-13 |
| US20200046740A1 (en) | 2020-02-13 |
| US11229657B2 (en) | 2022-01-25 |
| US20220096502A1 (en) | 2022-03-31 |
| EP3612177A1 (fr) | 2020-02-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20220096502A1 (en) | Targeting hypoxic cancer stem cells (cscs) with doxycycline: implications for improving anti-angiogenic therapy | |
| De Francesco et al. | Targeting hypoxic cancer stem cells (CSCs) with Doxycycline: Implications for optimizing anti-angiogenic therapy | |
| Sun et al. | Metallothionein‐1G facilitates sorafenib resistance through inhibition of ferroptosis | |
| Wang et al. | Branched-chain amino acid aminotransferase 2 regulates ferroptotic cell death in cancer cells | |
| EP3612187B1 (fr) | Vitamine c et doxycycline : polythérapie létale synthétique pour éradiquer des cellules souches cancéreuses (cscs) | |
| Liu et al. | NRF2 regulates the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via FOCAD-FAK signaling pathway | |
| Demidenko et al. | Pharmacologic inhibition of MEK and PI-3K converges on the mTOR/S6 pathway to decelerate cellular senescence | |
| US11559527B2 (en) | Targeting mitochondrial fission through mDIVI-1 derivatives | |
| Ye et al. | Frenolicin B targets peroxiredoxin 1 and glutaredoxin 3 to trigger ROS/4E-BP1-mediated antitumor effects | |
| He et al. | Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells | |
| Shen et al. | PARPi treatment enhances radiotherapy-induced ferroptosis and antitumor immune responses via the cGAS signaling pathway in colorectal cancer | |
| Boesch‐Saadatmandi et al. | Ochratoxin A impairs Nrf2‐dependent gene expression in porcine kidney tubulus cells | |
| Myers | Enhanced targeting of mitochondrial peroxide defense by the combined use of thiosemicarbazones and inhibitors of thioredoxin reductase | |
| Fan et al. | Zinc inhibits high glucose-induced NLRP3 inflammasome activation in human peritoneal mesothelial cells | |
| Czarnecka et al. | Alterations in the expression of nNOS in the substantia nigra and subthalamic nucleus of 6-OHDA-lesioned rats: the effects of chronic treatment with l-DOPA and the nitric oxide donor, molsidomine | |
| US20230040965A1 (en) | Energetic cancer stem cells (e-cscs): a new hyper-metabolic and proliferative tumor cell phenotype, driven by mitochondrial energy | |
| Song et al. | The enhancement of Tetrandrine to gemcitabine-resistant PANC-1 cytochemical sensitivity involves the promotion of PI3K/Akt/mTOR-mediated apoptosis and AMPK-regulated autophagy | |
| Zhang et al. | Arginase 1 expression is increased during hepatic stellate cell activation and facilitates collagen synthesis | |
| Jiang et al. | A CRISPR screen identifies redox vulnerabilities for KEAP1/NRF2 mutant non-small cell lung cancer | |
| Hayman et al. | Competitive but not allosteric mTOR kinase inhibition enhances tumor cell radiosensitivity | |
| Fang et al. | RMI1 contributes to DNA repair and to the tolerance to camptothecin | |
| Tang et al. | Fangchinoline accumulates autophagosomes by inhibiting autophagic degradation and promoting TFEB nuclear translocation | |
| Jin et al. | Antiproliferative activity and therapeutic implications of potassium tris (4-methyl-1-pyrazolyl) borohydride in hepatocellular carcinoma | |
| Qiu et al. | Activation Ferroptosis Enhanced the Therapy Sensitivity of TNBC to Paclitaxel Via NCOA4 Mediated Ferritinophagy | |
| Chai et al. | Bleomycin restricts the glycolysis of lymphatic endothelial cells by inhibiting dimeric PKM2 formation: A novel mechanism for lymphatic malformation treatment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220214 |
|
| EEER | Examination request |
Effective date: 20220214 |
|
| EEER | Examination request |
Effective date: 20220214 |
|
| EEER | Examination request |
Effective date: 20220214 |
|
| EEER | Examination request |
Effective date: 20220214 |
|
| EEER | Examination request |
Effective date: 20220214 |
|
| EEER | Examination request |
Effective date: 20220214 |